Conventional drug delivery today most commonly involves either drug injection into a biological body, or tablet or liquid intake from the mouth. Each of these delivery approaches are non-selective, external, uncontrolled and highly prone to interactions with various chemical and biological components within the biological system prior to the drug reaching its target sites. This non-selective approach means that in certain treatments (such as cancer treatment), both healthy cells and unhealthy cells (such as cancer cells) are equally exposed to the same drug at the same dosage. Such external and uncontrolled approaches provide a long pathway from the point at which the drug is introduced into the system and where it is actually applied to its targeted site. Also, the drug dosage cannot be precisely controlled since the drug's concentration may change along the biological pathway from the introduction point to the targeted site due to many factors which include but are not limited to metabolism. In fact, there are no current methodologies which determine, in real time, the degree of drug adsorption or absorption at the targeted site on a microscopic level in a living biological system.
Traditional drug delivery methods have been mainly limited to liquid injection and administration (in tablet or capsule form) in-take through the mouth. In recent years, nano-particles have been proposed and evaluated for drug delivery applications, mostly involving carrying drugs inside or on the surface of such nano-particles. [See S. D. Smedt, J. Am. Chem. Soc. 130, pp. 14480-14482 (2008); A. L. Z. Lee, et al., Biomaterials, 30, pp. 919-927 (2009); T. Desai, Nano Lett. 9, pp. 716-720 (2009); R. O. Esenaliev, U.S. Pat. No. 6,165,440; P. S. Kumar, et al., U.S. Pat. No. 7,182,894; C. J. O'Conner, et al., US Patent Application#20020068187; S. A. Herweck, et al., US Patent Application#20040236278; H. Hirata, et al., US Patent Application#20070243401; G. S. Yi, et al., US Patent Application#2009008146].
For example, A. Chauhan, et al., disclosed a drug delivery system comprising a contact lens in which nano-particles are dispersed with drug encapsulated in the said nano-particles (See US Patent Application #20040096477). Most of the proposed approaches using nano-particles lack the following basic functions and abilities: (a) to reach its targets location in a controlled manner, (b) selectivity and specificity to its intended targets (such as cancer cells), (c) the ability to avoid interactions with the environment on its way to its intended target(s), (d) a controlled release mechanism at a microscopic level (for example, releasing drug only to a specific cell and not to its surrounding area), and (e) bio-degradability of the nano-particle after its use. Very few have contemplated approaches which selectively target treatment sites. J. S. Minor, et. al. (US patent application #20060040390) proposed the use of a biological “key” molecule to recognize targets. A. Manganaro, et al. proposed a method (US patent application #20080279764) in which an ascorbate on the surface of nano-carrier is used to react with the super oxides produced by the cells, with an expected result of enhanced reactions between anti-cancer agent in the carrier and the cancer cells. While the above mentioned prior art attempts to target treatment, the applicability is relatively narrow and lacks the ability to target a wide range of cells/tissues/organs and diseases. Further, the “key” molecule or ascorbate on the surface of nano-carriers mentioned in the Minor and Manganaro applications are likely to react with the environment in the living body and will thus have many difficulties in reaching its intended targets while still in its original form.
In addition to the above stated limitations, the prior art drug delivery approaches also appear to lack general applicability and practicality. The novel drug delivery method disclosed in the current application overcomes the above-mentioned limitations and problems in the prior art. The current, disclosed method has multiple, clearly and strongly differentiated innovations in its integrated drug delivery system which is capable of positioning, sensing (microscopic properties of cells, tissues, and organs), analyzing, logic decision making, drug storage, and drug releasing in a controlled, targeted, and microscopic manner. The disclosed targeted treatment is achieved via measurements of microscopic parameters including but not limited to surface charge, surface voltage, resting potential, absorption and adsorption properties, local pH, Local chemical compositions, local biological compositions and cell compositions. The integrated micro-carrier for drug delivery is fabricated using techniques in microelectronics, with various components including positioning, sensing, analyzing, logic processing, and drug storage and drug release units integrated onto the same chip.
The problems discussed above in today's drug delivery approaches may be responsible for the relatively large discrepancy between laboratory drug tests and clinic drug trials, where many promising drugs in laboratory tests (on animals such as rats) which show clinical efficacy have been proven ineffective in human tests. Further, for diseases such as cancer, nearly all drugs have been ineffective and/or toxic to the human body. To date, there is no technology enabling a direct and selective drug delivery directly to a targeted site within the biological system. It is highly possible that most of the drugs in the existing application techniques have various degree of interaction with various chemical and biological components in a live biological system that negatively affects the drug's efficacy. In the case of treatment utilizing cancer drugs, even if the drug reaches its targeted cancer cells, its strength (concentration) and chemical composition could have been altered, rendering the drug relatively ineffective. Further, there have been no drug delivery methodologies which can be delivered at the cellular level (such as a desired drug injection into a cell through the cell membrane) with controllability and selectivity. Finally, detailed reaction mechanisms as well as absorption/adsorption issues between the drug and its targeted site are not fully understood in a live biological system.
Many cancer treatment drugs have not shown their expected promising results in human trials, even though tests on laboratory animals have shown to be successful. The inventors of this method believe that there are major issues relating to successful and effective drug delivery to the targeted cancer cells. Since such drugs are often taken in tablet/capsule, liquid form (via oral intake) or injection into the biological system, there exist serious issues in reaching the targeted cancer sites in a controlled and effective manner.
For both disease prevention and treatment purposes in modern medicine, there is a critical and urgent need to significantly improve the current drug delivery methodology and approach.